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Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 7890

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Special Issue Editor

Dr. Denis N. Silachev

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Guest Editor

1. Laboratory of Biochemistry of Motor Systems, A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia
2. Laboratory Stem Cells Technology, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia
Interests: extracellular vesicles; cerebral ischemia; stroke; brain trauma; mitochondrial traffic; neuroprotection; ischemic preconditioning; autophagy; aging; intercellular communication
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Special Issue Information

Dear Colleagues,

Extracellular vesicles are currently one of the most widely studied cellular derivatives in terms of various aspects of cellular physiology, and they are considered to represent a new mode of intercellular communication. Extracellular vesicles are commonly found, and the term refers to a heterogeneous group of cell-derived membranous structures that includes exosomes and microvesicles. In spite of this, the methodology used for isolating cellular vesicles has not yet been standardized. Additionally, it is difficult to separate the studied objects by origin based only on linear dimensions and their mass due to overlap in these parameters. The possibility of using extracellular vesicles of stem/progenitor and somatic cells as therapeutic tools with a wide range of cytoprotective and regenerative properties has been convincingly demonstrated. This has prompted the search for “therapeutic” molecules in extracellular vesicles. However, this task is complicated by the complex composition of extracellular vesicles, which includes lipids, proteins, and nucleic acids. The results of the existing research are also contradictory, with some studies demonstrating the key role of miRNA, while others completely exclude the contribution of miRNA to the signaling/therapeutic effects of extracellular vesicles. The fundamental question is understanding the contribution of lipids, proteins, and microRNA, which will determine further strategies for creating biomedical drugs based on extracellular vesicles.

In this regard, we invite researchers to contribute original research articles and review articles that will stimulate continuing efforts to understand the role of lipids, proteins, or nucleic acids in the observed therapeutic effects, alone or in combination. Submissions from studies aiming to create cellular model systems that allow for the targeted control of the cargo of extracellular vesicles will be welcomed. Also of interest are submissions on the use of inhibitory analysis and omics technologies with bioinformatics analysis to identify signaling pathways in recipient cells and molecules in extracellular vesicles involved in therapeutic effects.

Dr. Denis N. Silachev
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

exosomes
ectosomes
vesicles
lipids
proteins
nucleic acids
drug delivery
stem cell
regenerative therapeutics

Published Papers (5 papers)

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Research

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15 pages, 4177 KiB

Open AccessCommunication

Extracellular Vesicles Produced by the Cardiac Microenvironment Carry Functional Enzymes to Produce Lipid Mediators In Situ

by Varravaddheay Ong-Meang, Muriel Blanzat, Lesia Savchenko, Lucie Perquis, Mégane Guardia, Nathalie Pizzinat and Verena Poinsot

Int. J. Mol. Sci. 2023, 24(6), 5866; https://doi.org/10.3390/ijms24065866 - 20 Mar 2023

Cited by 2 | Viewed by 1348

Abstract

The impact of the polyunsaturated fatty acids (PUFAs) at physiological concentrations on the composition of eicosanoids transported within the extracellular vesicles (EVs) of rat bone marrow mesenchymal stem cells and cardiomyoblasts was reported by our group in 2020. The aim of this article was to extend this observation to cells from the cardiac microenvironment involved in the processes of inflammation, namely mouse J774 macrophages and rat heart mesenchymal stem cells cMSCs. Moreover, to enhance our capacity to understand the paracrine exchange between these orchestrators of cardiac inflammation, we investigated some machinery involved in the eicosanoid’s synthesis transported by the EVs produced by these cells (including the two formerly described cells: bone marrow mesenchymal stem cells BM-MSC and cardiomyoblasts H9c2). We analyzed the oxylipin and the enzymatic content of the EVs collected from cell cultures supplemented (or not) with PUFAs. We prove that large eicosanoid profiles are exported in the EVs by the cardiac microenvironment cells, but also that these EVs carry some critical and functional biosynthetic enzymes, allowing them to synthesize inflammation bioactive compounds by sensing their environment. Moreover, we demonstrate that these are functional. This observation reinforces the hypothesis that EVs are key factors in paracrine signaling, even in the absence of the parent cell. We also reveal a macrophage-specific behavior, as we observed a radical change in the lipid mediator profile when small EVs derived from J774 cells were exposed to PUFAs. To summarize, we prove that the EVs, due to the carried functional enzymes, can alone produce bioactive compounds, in the absence of the parent cell, by sensing their environment. This makes them potential circulating monitoring entities. Full article

(This article belongs to the Special Issue Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0)

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Review

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35 pages, 2449 KiB

Open AccessReview

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

by Kirill Goryunov, Mikhail Ivanov, Andrey Kulikov, Yulia Shevtsova, Artem Burov, Yulia Podurovskaya, Victor Zubkov, Dmitry Degtyarev, Gennady Sukhikh and Denis Silachev

Int. J. Mol. Sci. 2024, 25(5), 2879; https://doi.org/10.3390/ijms25052879 - 1 Mar 2024

Viewed by 1079

Abstract

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic–ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice. Full article

(This article belongs to the Special Issue Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0)

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21 pages, 1372 KiB

Open AccessReview

Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases

by Jialing Wu, Gege Liu, Rong Jia and Jihua Guo

Int. J. Mol. Sci. 2023, 24(24), 17328; https://doi.org/10.3390/ijms242417328 - 10 Dec 2023

Cited by 1 | Viewed by 1363

Abstract

Extracellular vesicles, as bioactive molecules, have been extensively studied. There are abundant studies in the literature on their biogenesis, secretion, structure, and content, and their roles in pathophysiological processes. Extracellular vesicles have been reviewed as biomarkers for use in diagnostic tools. Saliva contains many extracellular vesicles, and compared with other body fluids, it is easier to obtain in a non-invasive way, making its acquisition more easily accepted by patients. In recent years, there have been numerous new studies investigating the role of salivary extracellular vesicles as biomarkers. These studies have significant implications for future clinical diagnosis. Therefore, in this paper, we summarize and review the potential applications of salivary extracellular vesicles as biomarkers, and we also describe their other functions (e.g., hemostasis, innate immune defense) in both oral and non-oral diseases. Full article

(This article belongs to the Special Issue Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0)

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27 pages, 1690 KiB

Open AccessReview

The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches

by Eleni-Myrto Trifylli, Anastasios G. Kriebardis, Evangelos Koustas, Nikolaos Papadopoulos, Sofia Vasileiadi, Sotirios P. Fortis, Vassilis L. Tzounakas, Alkmini T. Anastasiadi, Panagiotis Sarantis, Effie G. Papageorgiou, Ariadne Tsagarakis, Georgios Aloizos, Spilios Manolakopoulos and Melanie Deutsch

Int. J. Mol. Sci. 2023, 24(21), 15563; https://doi.org/10.3390/ijms242115563 - 25 Oct 2023

Cited by 4 | Viewed by 1546

Abstract

Cholangiocarcinomas (CCAs) constitute a heterogeneous group of highly malignant epithelial tumors arising from the biliary tree. This cluster of malignant tumors includes three distinct entities, the intrahepatic, perihilar, and distal CCAs, which are characterized by different epidemiological and molecular backgrounds, as well as prognosis and therapeutic approaches. The higher incidence of CCA over the last decades, the late diagnostic time that contributes to a high mortality and poor prognosis, as well as its chemoresistance, intensified the efforts of the scientific community for the development of novel diagnostic tools and therapeutic approaches. Extracellular vesicles (EVs) comprise highly heterogenic, multi-sized, membrane-enclosed nanostructures that are secreted by a large variety of cells via different routes of biogenesis. Their role in intercellular communication via their cargo that potentially contributes to disease development and progression, as well as their prospect as diagnostic biomarkers and therapeutic tools, has become the focus of interest of several current studies for several diseases, including CCA. The aim of this review is to give a rundown of the current knowledge regarding the emerging role of EVs in cholangiocarcinogenesis and their future perspectives as diagnostic and therapeutic tools. Full article

(This article belongs to the Special Issue Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0)

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18 pages, 977 KiB

Open AccessReview

The Therapeutic Potential of Multipotent Mesenchymal Stromal Cell—Derived Extracellular Vesicles in Endometrial Regeneration

by Gyuzyal Tabeeva, Denis Silachev, Polina Vishnyakova, Alexandra Asaturova, Timur Fatkhudinov, Antonina Smetnik and Madina Dumanovskaya

Int. J. Mol. Sci. 2023, 24(11), 9431; https://doi.org/10.3390/ijms24119431 - 29 May 2023

Cited by 6 | Viewed by 1864

Abstract

Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions underlie the development of “thin” endometrium and/or Asherman’s syndrome (AS) and are a common cause of infertility and a high risk for adverse obstetric outcomes. The methods used (surgical adhesiolysis, anti-adhesive agents, and hormonal therapy) do not allow restoration of the regenerative properties of the endometrium. The experience gained today with cell therapy using multipotent mesenchymal stromal cells (MMSCs) proves their high regenerative and proliferative properties in tissue damage. Their contribution to regenerative processes is still poorly understood. One of these mechanisms is based on the paracrine effects of MMSCs associated with the stimulation of cells of the microenvironment by secreting extracellular vesicles (EVs) into the extracellular space. EVs, whose source is MMSCs, are able to stimulate progenitor cells and stem cells in damaged tissues and exert cytoprotective, antiapoptotic, and angiogenic effects. This review described the regulatory mechanisms of endometrial regeneration, pathological conditions associated with a decrease in endometrial regeneration, and it presented the available data from studies on the effect of MMSCs and their EVs on endometrial repair processes, and the involvement of EVs in human reproductive processes at the level of implantation and embryogenesis. Full article

(This article belongs to the Special Issue Study of the Molecular Mechanisms of the Therapeutic Properties of Extracellular Vesicles 2.0)

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